Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside
Background: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aime...
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MDPI AG
2020-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/8/12/577 |
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| author | Mattan Levi Tal Goshen-Lago Rinat Yerushalmi Tal Granot Salomon M. Stemmer Ruth Shalgi Irit Ben-Aharon |
| author_facet | Mattan Levi Tal Goshen-Lago Rinat Yerushalmi Tal Granot Salomon M. Stemmer Ruth Shalgi Irit Ben-Aharon |
| author_sort | Mattan Levi |
| collection | DOAJ |
| description | Background: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aimed to study the effect of anti-HER2/neu on chemotherapy-induced ovarian toxicity in both clinical and preclinical settings. Methods: We prospectively enrolled breast cancer patients below the age of 42 years who were treated with chemotherapy with or without trastuzumab into the study. Anti-Müllerian hormone (AMH) was measured 6 and 12 months post-chemotherapy as an ovarian reserve indicator. In the animal model, pubertal mice were injected with cyclophosphamide or paclitaxel with or without anti-HER2/neu, or saline, and sacrificed 1 week or 3 months later. Ovarian apoptosis, proliferation and vascularity were measured by immunohistochemistry and ovarian reserve was measured by morphometric analysis and serum-AMH. Results: Thirty-three patients with early breast cancer were enrolled into the study. Nineteen patients had HER2/neu negative cancer and were treated with chemotherapy and 14 had HER2/neu positive cancer and were treated with chemotherapy and trastuzumab. In all patients, AMH levels declined to undetectable values immediately post-treatment, but regained for 57.1% of the HER2/neu positive cohort and 36.8% of the negative cohort (<i>p</i> < 0.05). In the preclinical setting, anti-HER2/neu antibody, in combination with chemotherapy, displayed lessened ovarian and vascular damage. Conclusions: Our results indicate that trastuzumab may alleviate chemotherapy-induced ovarian toxicity that may be mediated via its effect on ovarian vasculature. |
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| language | English |
| last_indexed | 2024-03-10T14:16:30Z |
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| series | Biomedicines |
| spelling | doaj.art-5f09a06520654286bdc592e7609e844a2023-11-20T23:43:35ZengMDPI AGBiomedicines2227-90592020-12-0181257710.3390/biomedicines8120577Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to BedsideMattan Levi0Tal Goshen-Lago1Rinat Yerushalmi2Tal Granot3Salomon M. Stemmer4Ruth Shalgi5Irit Ben-Aharon6Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelDivision of Oncology, Rambam Health Care Campus, Haifa 3109601, IsraelInstitute of Oncology, Davidoff Center, Beilinson Campus, Rabin Medical Center, Petah-Tiqva 49100, IsraelInstitute of Oncology, Davidoff Center, Beilinson Campus, Rabin Medical Center, Petah-Tiqva 49100, IsraelInstitute of Oncology, Davidoff Center, Beilinson Campus, Rabin Medical Center, Petah-Tiqva 49100, IsraelDepartment of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, IsraelDivision of Oncology, Rambam Health Care Campus, Haifa 3109601, IsraelBackground: Trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, is considered a standard treatment in addition to chemotherapy in the adjuvant setting for HER2/neu-positive breast cancer, yet its impact on fertility and ovarian reserve remains obscure. We aimed to study the effect of anti-HER2/neu on chemotherapy-induced ovarian toxicity in both clinical and preclinical settings. Methods: We prospectively enrolled breast cancer patients below the age of 42 years who were treated with chemotherapy with or without trastuzumab into the study. Anti-Müllerian hormone (AMH) was measured 6 and 12 months post-chemotherapy as an ovarian reserve indicator. In the animal model, pubertal mice were injected with cyclophosphamide or paclitaxel with or without anti-HER2/neu, or saline, and sacrificed 1 week or 3 months later. Ovarian apoptosis, proliferation and vascularity were measured by immunohistochemistry and ovarian reserve was measured by morphometric analysis and serum-AMH. Results: Thirty-three patients with early breast cancer were enrolled into the study. Nineteen patients had HER2/neu negative cancer and were treated with chemotherapy and 14 had HER2/neu positive cancer and were treated with chemotherapy and trastuzumab. In all patients, AMH levels declined to undetectable values immediately post-treatment, but regained for 57.1% of the HER2/neu positive cohort and 36.8% of the negative cohort (<i>p</i> < 0.05). In the preclinical setting, anti-HER2/neu antibody, in combination with chemotherapy, displayed lessened ovarian and vascular damage. Conclusions: Our results indicate that trastuzumab may alleviate chemotherapy-induced ovarian toxicity that may be mediated via its effect on ovarian vasculature.https://www.mdpi.com/2227-9059/8/12/577ovarian toxicitychemotherapyanti-HER2/neutrastuzumab |
| spellingShingle | Mattan Levi Tal Goshen-Lago Rinat Yerushalmi Tal Granot Salomon M. Stemmer Ruth Shalgi Irit Ben-Aharon Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside Biomedicines ovarian toxicity chemotherapy anti-HER2/neu trastuzumab |
| title | Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside |
| title_full | Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside |
| title_fullStr | Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside |
| title_full_unstemmed | Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside |
| title_short | Anti-HER2/neu Antibody Reduces Chemotherapy-Induced Ovarian Toxicity—From Bench to Bedside |
| title_sort | anti her2 neu antibody reduces chemotherapy induced ovarian toxicity from bench to bedside |
| topic | ovarian toxicity chemotherapy anti-HER2/neu trastuzumab |
| url | https://www.mdpi.com/2227-9059/8/12/577 |
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